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Preterm births still a mystery

Though they have improved at identifying women who might be at risk, doctors are still trying to figure out how to prevent premature births

In the Neonatal Intensive Care Unit at Tufts Medical Center, Tanya Ianniello checked on her 16-day-old daughter, Ruby, who was born prematurely. In the Neonatal Intensive Care Unit at Tufts Medical Center, Tanya Ianniello checked on her 16-day-old daughter, Ruby, who was born prematurely. (WENDY MAEDA/GLOBE STAFF)
By Deborah Kotz
Globe Staff / December 19, 2011
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In a bustling unit at Tufts Medical Center lie 25 of the tiniest humans in Boston - one weighing in at just 1 pound, 3 ounces. Photos adorn the walls of the neonatal intensive care unit, showing previous patients with dimples, sparkling eyes, and wide smiles, thriving in preschool or elementary school. You would never know they were once tethered to heart monitors and feeding tubes after tumbling out of the womb two or even three months too soon.

No doubt, these photos - and a report published last week in the journal Pediatrics, documenting healthy outcomes for two of the world’s smallest babies, born weighing less than 9 ounces each - provide much needed hope to parents of premature infants. But they also belie the fact that despite lifesaving medical advances, doctors are unable to prevent most premature births from occurring in the first place.

For every success story, there are tales of irreversible health problems such as cerebral palsy, developmental delays, impaired vision, and chronic lung disease, with one in four premature infants - defined as those born before 37 weeks - experiencing lifelong problems that result from early birth.

Doctors counsel women with vaginal bleeding, early contractions, or cervical abnormalities to stay in bed, take time off work, and minimize stress, despite real evidence that these measures work, according to Dr. Errol Norwitz, chair of obstetrics and gynecology at Tufts Medical Center.

Herculean efforts to prevent preterm births have resulted only in modest progress: the nation’s preterm birth rate has declined a bit over the past four years, slipping to under 12 percent of total births for the first time in nearly a decade after steadily rising to a peak of nearly 13 percent, according to a November report issued by the National Center for Health Statistics. But more than half a million premature births still occur every year at an annual cost to the US health care system of $26 billion. (The average medical costs incurred by a healthy full-term baby through the first year of life is slightly less than $5,000, compared with $50,000 for a premature infant.)

“We’ve gotten much better at determining who’s most at risk of preterm birth, but have made little headway at preventing it,’’ said Norwitz.

Some headway has been made at preventing known risks such as vaginal infections and smoking. And Massachusetts is doing somewhat better than other states, with a preterm birth rate just under 11 percent, likely because of its smoking cessation programs and universal health coverage, public health specialists speculate. But it also faces unique challenges.

Massachusetts has one of the highest birth rates of twins and triplets, who are often born premature, since the state mandates health insurance coverage for in vitro fertilization. And more than 30 percent of babies born in Massachusetts are to women over age 35, who are at higher risk of delivering early; about double the national average, said Dr. Diana Bianchi, neonatologist and executive director of the Tufts Mother Infant Research Institute.

Maternal obesity - which occurs in nearly 1 in 5 pregnant women today compared with 1 in 14 during the 1980s - has led to more premature births as well. Determining ways to limit weight gain in obese pregnant women, Bianchi said, has become a key area of research at Tufts.

By far, though, the biggest barrier to reducing preterm births lies in determining causes for the vast majority of cases, which currently remain a mystery. “Women can do everything right and still deliver early,’’ said Dr. Jennifer Howse, president of the March of Dimes. The organization partnered with Stanford University School of Medicine last March to open a research center dedicated to finding the causes of preterm births.

“We’re taking an entirely different approach, looking at causes no one has explored like weather patterns, crime statistics where women live, genetic markers, and characteristics of the placenta and how these things all may interact with each other,’’ said Stanford neonatologist Dr. Gary Shaw.

For now, doctors have scant tools at their disposal to prevent early deliveries. A progesterone injection called Makena that was approved by the US Food and Drug Administration last February can reduce the rate of preterm births by about a third in women who have had previous premature births. “The magnitude of the effect is modest,’’ said Dr. Michael Greene, chief of obstetrics at Mass. General. “But we don’t have anything that’s better.’’ Anti-contraction drugs called tocolytics can suppress labor by a day or two once the cervix begins to dilate, barely long enough to administer steroids to help a baby’s lungs mature.

All too often, doctors find themselves practicing art more than medicine in helping women prolong their pregnancies. Norwitz and his colleagues at Tufts often measure the length of a woman’s cervix during a standard ultrasound screening that typically occurs at around 18 to 20 weeks of pregnancy. A short cervix on ultrasound is a major risk factor for premature birth even for those with no other risk factors who are pregnant for the first time.

“Studies suggest that only 2 percent of women will have a cervical length of less than 1.5 centimeters halfway through their pregnancy,’’ said Norwitz. “But of these, 60 percent will deliver by 28 weeks, and 90 percent by 34 weeks.’’ The American College of Obstetricians and Gynecologists doesn’t recommend the cervical measurement test for routine use in its practice guidelines despite its usefulness as “a predictor of preterm labor’’ because of “a lack of proven treatments affecting outcome.’’

Tufts patient Tameka Mills was told six weeks ago that she had a high risk of delivering prematurely after an ultrasound revealed her cervix to be short. Twenty-four weeks pregnant as of late last week, Mills has been taking vaginal progesterone suppositories and also had a stitch, called a cerclage, placed around her cervix in an effort to keep it closed. Although she has two sons born at full term, Mills said she’s nervous this time around because she also had a previous miscarriage at 16 weeks.

“We decided not to give her Makena since it’s only approved for women who had previous preterm births,’’ said Dr. Linda Kleeman, one of the Tufts obstetricians treating Mills, but studies suggest progesterone applied vaginally may be effective in preventing preterm birth for women with short cervixes. An analysis of five studies published last week in the American Journal of Obstetrics and Gynecology found that it reduced the risk of delivering before 28 weeks by about half in these women compared with a placebo and reduced the risk of delivering before 35 weeks by about 30 percent. The studies on cerclage have had mixed results but Norwitz said, “we’re hoping that using the two together will improve the odds’’ of prolonging Mills’s pregnancy.

So far, though, it doesn’t seem to be working. At Mills’s appointment last week, her cervix had shortened and thinned from 2.1 centimeters - before she had any treatment - down to 1.4. If things progress further, she may have to be hospitalized and the fetus treated with steroids to prepare for early delivery. “At this point, the baby is just at the point of viability and her prognosis is still very guarded,’’ said Kleeman.

Meanwhile, Mills dutifully follows what her doctors advised: “I was told to stay in bed and not to do a lot of walking,’’ she said. Norwitz said he wasn’t surprised to hear Mills had gotten these instructions at Tufts. “I give this advice all the time,’’ he said. “Women want something they can do.’’ It might help them feel some semblance of control over a frightening situation, he added, even though “it’s not evidence-based medicine.’’

Deborah Kotz can be reached at dkotz@globe.com. Follow her on Twitter @debkotz2.

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